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Summary: Invasive dental procedures performed in the standing, sedated horse are facilitated by local and regional anaesthesia. The traditional transcutaneous approach to the mental foramen is used to desensitise the incisive region including the mandibular incisors, but is not well tolerated by many sedated patients. In this study, a new, intraoral needle insertion technique for nerve block at the mental foramen was investigated. In 15 equine cadaver heads and two live horses, computed tomography (CT) was used to verify Tuohy needle placement into each mental foramen using an intraoral technique. Varying volumes of contrast medium (3, 6, 10 mL) were injected into the mandibular canal with and without digital occlusion of the mental foramen. The distance of retrograde flow was measured. Additionally, measurements were taken to determine the position of the mental foramen within the interdental space. Correct placement of Tuohy needles and injection of contrast medium into the mandibular canal using an intraoral approach at the mental foramen was achieved in all injections. Retrograde flow of contrast medium was accomplished with all volumes, regardless of occlusion. Although not statistically significant, the 10 mL group appeared to have a greater distance of flow. The needle insertion technique described here appears to be a potential alternative to traditional transcutaneous approaches to mental nerve block for procedures involving the incisive region. In addition, it was found that 79% of the mandibular canals injected with 10 mL of contrast medium had retrograde flow to the position of PM4, suggesting this method may be a useful alternative technique for nerve block for the more rostrally located cheek teeth. The location of the mental foramen was consistently found in the distal third of the interdental space (approximately 60–80% of the distance between the distal aspect of the lateral corner incisor and the mesial aspect of the second premolar). [ABSTRACT FROM AUTHOR]

The ischemia induced vasospasm of the renal arterial blood vessels mediated by α1-adrenoceptors is of importance for the loss of kidney function. This is based on reduced perfusion of the kidney cortex occuring in kidney transplant and organ preserving surgery. The present study considered the intracellular mechanism of the norepinephrine (NE) induced renal artery vasospasm by using swine renal artery smooth muscle ring. Norepinephrine and phenylephrine (PE) induced dose-dependent and fully reversible isometric contractions with a threshold concentration of 10 nM (n=7) and 10 nM (n=4), and an EC50 of 0.3 μM and 1 μM, respectively. The receptor was identified as α1A-subtype. The contraction was completely inhibited by verapamil (IC50=1.51 μM; n=11) and diltiazem (IC50=9.49 μM; n=8) and 85% by nifedipine (IC50=0.13 μM; n=21). Blockade of the intracellular inositol-1,4,5-trisphosphate (IP3)-sensitive Ca2+ store by thapsigargin (1 μM, n=7) or suppression of Ca2+ release from the intracellular Ca2+-sensitive Ca2+ store by ryanodine (100 μM, n=4) inhibited the PE induced contraction by 39.5% and 47.6%, respectively. The results suggest a key role of voltage-dependent Ca2+ channels and intracellular Ca2+ stores in the α1A-adrenoceptor induced contraction of the renal artery. [ABSTRACT FROM AUTHOR]

Objective: To determine the participation of GTP-binding proteins (G-proteins) in the cellular mechanism of the phenylephrine-induced renal artery vasospasm by using swine renal artery smooth muscle rings in a standard organ baths, as increased noradrenaline release from perivasal and intramural sympathetic nerve endings during renal ischaemia results in increased vascular smooth muscle tone that is important in the loss of kidney function during renal transplantation and nephron-sparing surgery., Materials and Methods: Fresh swine kidneys were transported in cold calcium-free Tyrode solution to the laboratory. Adipose tissue around the arteries was removed, the organ de-capsulated and interlobar arteries dissected. The contractile properties of renal artery smooth muscle rings were assessed in a standard organ bath, the rings pre-tensioned at 2 g. Contractions were evoked by applying the alpha 1-adrenoceptor selective agonist phenylephrine (1 nmol/L to 0.3 mmol/L). Isometric contractions of the tissue were registered and stored digitally. Dose-response curves were obtained sequentially with a wash-out of 20 min between each concentration; the maximum contractility of an individual muscle ring was set at 100%. Dose-response curves of inhibitory agents (e.g. WB4101, cholera and pertussis toxins) were determined by comparing the remaining contractility after incubating with the respective drug with a control contraction that was evoked three times (10 mumol/L phenylephrine) and the mean set at 100%., Results: Phenylephrine induced dose-dependent and fully reversible isometric contractions with a threshold concentration of 100 nmol/L and an EC50 of 0.8 mumol/L. The receptor was identified as the alpha 1A-subtype by the selective antagonist WB4101. Pre-treatment of tissue rings with 5 micrograms/mL pertussis toxin (120 min, 37 degrees C) inhibited the control contraction by a mean (SEM) of 52.0 (4.6)%, whereas pre-treatment with 1 microgram/mL cholera toxin (60 min, 37 degrees C), leading to a permanent activation of the Gs-protein via blockade of the GTPase activity, decreased the response by 39.0 (8.2%)., Conclusion: These results suggest a coupling of alpha 1A-adrenoceptors in renal vascular tissue to the heterotrimeric Gs-protein and to heterotrimeric G-proteins of the G1- and/or G0-family in the phenylephrine-induced contraction.

The elevation of vascular smooth muscle tone in the renal arteries during kidney transplantation and nephron-sparing surgery plays a major role in postsurgical organ dysfunction. Therefore, a better understanding of the intracellular mechanisms of contraction and relaxation is of fundamental interest to improve urological treatment. The present study was designed to investigate the complex intracellular system of cyclic nucleotides involved in the regulation of smooth muscle relaxation by using swine renal artery rings in the Schuler organ bath. Phenylephrine (PE) induced dose-dependent and fully reversible isometric contractions with a threshold concentration of 10 nM and an EC(50) of 804 nM. The receptor was identified as alpha(1A)-subtype by the selective antagonist WB4101. Increasing the intracellular concentration of cyclic 3':5'-adenosine monophosphate (cAMP) by dibutyryl-cAMP (5 mM) and forskolin (5 micro M) resulted in a decreased contractiltity of 48.0% and 76.3%, respectively. Elevation of the cytosolic content of cyclic 3':5'-guanosine monophosphate (cGMP) using dibutyryl-cGMP (1 mM), sodium nitroprusside (100 micro M) and SIN-1 (100 micro M) decreased the average PE-induced contraction by 16.4%, 41.9% and 62.4%, respectively. The unselective phosphodiesterase inhibitors theophylline (1 mM), papaverine (100 micro M) and IBMX (5 mM) reduced the PE-induced contraction by 37.3%, 93.1% and 95.5%, respectively. Furthermore, selective inhibition of phosphodiesterases by milrinone (PDE(3)-selective) resulted in a decreased contractility by 1.3% (50 micro M), 29.5% (100 micro M) and 93.5% (5 mM), and using rolipram (PDE(4) selective), the PE-induced contraction was inhibited by 57.9% (50 micro M) and 81.9% (100 micro M). The results suggest the involvement of cAMP and cGMP in the relaxation of renal artery smooth muscle cells. Moreover, phosphodiesterases, especially PDE(3) and PDE(4), seem to play a critical role in the regulation of renal artery smooth muscle tone.

Objective: The aim of the present study was to evaluate the therapeutic potency of an electrotherapy of striated ischiocavernous muscles in patients with erectile dysfunction., Patients and Methods: Transcutaneous electrostimulation of striated ischiocavernous muscles by self-adhesive penile or perineal skin electrodes was performed in 48 patients with erectile dysfunction. 6/48 patients (R) responded to intracavernous pharmacotherapy while 42/48 (NR) did not show significant penile rigidity even to intracavernous papaverine/phentolamine/PGE1 triple drug medication., Results: Within the observation time of 3 months, 10/48 patients dropped out. 22/38 patients reported a penile rigidity for sufficient sexual intercourse whereby 3/22 NR required additional intracavernous pharmacotherapy. Penile rigidity could be objectivated by triple drug medicaton in 12/14 NR after ischiocavernous muscle stimulation (EIS) therapy. 5/6 R were treated successfully for premature erection loss. During EIS treatment neither discomfort nor complications could be observed., Conclusion: Transcutaneous electrostimulation of ischiocavernous muscles is a new, noninvasive therapy for the improvement of penile rigidity. The clinical results underline the importance of the striated ischiocavernous muscles for penile rigidity.

The increased sympathetic neurotransmission in benign prostatic hyperplasia (BPH) results in a alpha 1C-adrenoceptor-mediated increase in prostatic smooth muscle tone which seems to be responsible for the dynamic infravesical obstruction occurring in BPH. The prostatic smooth muscle contractions evoked by norepinephrine can be efficiently blocked by alpha 1-adrenoceptor blockers. Moreover, an impressive number of clinical trials illustrated the beneficial results of alpha 1-adrenoceptor blockers in the treatment of BPH. However, despite knowledge of alpha 1-adrenergic neurotransmission and the clinical application of its blockade by selective alpha 1-adrenoceptor antagonists, very little is known about the intracellular pathways involved in the regulation of prostatic smooth muscle contractility. To study the intracellular mechanism of the alpha 1C-adrenoceptor-induced prostatic smooth muscle contraction, the patch-clamp technique in the whole-cell configuration mode combined with the Fura-II fluorescence technique was used in human, enzymatically isolated smooth muscle cells obtained from patients undergoing transurethral resection of the prostate because of symptomatic BPH. Furthermore changes in prostatic smooth muscle contractility were registered in organ bath experiments. Application of the selective alpha 1-adrenoceptor agonist phenylephrine (PE) increased the L-type Ca(2+)-channel current (ICa) dose dependently from 8 up to 18.5 microA/cm2, simultaneously elevating the free cytoplasmic Ca2+ concentration ([Ca2+]i) up to 1.9 microM. Pretreating the myocytes with pertussis toxin, an exotoxin of Bordetella pertussis which inactivates GTP-binding proteins (G proteins) of the Gi and G(o) family by ADP ribosylation, reduced the PE-induced ICa stimulation by 71.5 +/- 5.6% (n = 21). Dialysis of the cytosol with the second messenger inositol-1,4,5-trisphosphate (IP3), which releases Ca2+ from intracellular non-mitochondrial, IP3-sensitive Ca2+ pools, imitated the PE-evoked responses. Pretreating the myocytes with the Ca(2+)-release blockers ryanodine (10-100 microM, n = 8), thapsigargin (0.1 microM, n = 11) or low-molecular weight heparin (n = 14) largely attenuated the PE-evoked responses. The experimental results suggest a coupling of alpha 1-adrenoceptors to phospholipase C-converting phosphoinositol-4,5-bisphosphate into diacylglycerol, an endogenous activator of the protein kinase C and IP3 which releases Ca2+ from intracellular stores stimulating ICa via Ca(2+)-calmodulin-dependent protein kinase induced phosphorylation of voltage-dependent Ca2+ channels. This knowledge could be of interest for conservative treatment in symptomatic BPH.

Symptoms in benign prostatic hyperplasia (BPH) are partially caused by an increased prostatic smooth muscle tone. This tone depends on extra- and intracellular Ca2+ stores and is regulated by various second messenger pathways. We investigated the role of intracellular Ca2+ stores and cyclic 3'-5' adenosine monophosphate (cAMP) in BPH. Contractions elicited by the specific alpha 1-receptor agonist phenylephrine (PE) were inhibited by the selective alpha 1-receptor antagonists prazosin and YM 617. To elucidate the contribution of intracellular Ca2+ stores to the alpha 1-receptor induced contraction nifedipine, a blocker of voltage dependent L-type Ca2+ channels (VDCC) was applied and found to inhibit the PE induced contractions up to 65%. To further confirm the participation of intracellular Ca2+ stores, we applied ryanodine (10 microM) which reduced the alpha 1-receptor mediated contractions up to 80%. The remaining contraction was sensitive to nifedipine. The cAMP pathway mediating smooth muscle relaxation by regulating intracellular Ca2+ concentrations ([Ca2+]i) was also investigated. Nonspecific phosphodiesterase (PDE) inhibitors such as papaverine (0.5 mM) and theophylline (1 mM) and the specific PDE inhibitor milrinone (0.5 mM), all of which prevent degradation of cAMP, suppressed the PE induced contractions by 82%, 91% and 68%, respectively. Forskolin (50 microM), an activator of adenylylecyclase (AC), inhibited the PE induced contractions by 83%. The membrane permeable cAMP analog, N6-2'-0-dibutyryladenosine derivative (dBcAMP) also reduced the PE induced response by 70%.